Adebowale Adeyemo

Linkage and Association Analysis of Angiotensin I–Converting Enzyme (ACE)–Gene Polymorphisms with ACE Concentration and Blood Pressure

Considerable effort has been expended to determine whether the gene for angiotensin I-converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and association analysis of all the markers with ACE concentration. In multipoint variance-component analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE (P<.0013). The two most highly associated polymorphisms, ACE4 and ACE8, accounted for 6% and 19% of the variance in ACE, respectively. A two-locus additive model with an additive x additive interaction of these polymorphisms explained most of the ACE variation associated with this region. We next analyzed the relationship between these two polymorphisms (ACE4 and ACE8) and blood pressure (BP). Although no evidence of linkage was detected, significant association was found for both systolic and diastolic BP when a two-locus additive model developed for ACE concentration was used. Further analyses demonstrated that an epistasis model provided the best fit to the BP variation. In conclusion, we found that the two polymorphisms explaining the greatest variation in ACE concentration are significantly associated with BP, through interaction, in this African population sample. Our study also demonstrates that greater statistical power can be anticipated with association analysis versus linkage, when markers in strong linkage disequilibrium with a trait locus have been identified. Furthermore, allelic interaction may play an important role in the dissection of complex traits such as BP.

An international comparative study of blood pressure in populations of European vs. African descent

BackgroundThe consistent finding of higher prevalence of hypertension in US blacks compared to whites has led to speculation that African-origin populations are particularly susceptible to this condition. Large surveys now provide new information on this issue.MethodsUsing a standardized analysis strategy we examined prevalence estimates for 8 white and 3 black populations (N = 85,000 participants).ResultsThe range in hypertension prevalence was from 27 to 55% for whites and 14 to 44% for blacks.ConclusionsThese data demonstrate that not only is there a wide variation in hypertension prevalence among both racial groups, the rates among blacks are not unusually high when viewed internationally. These data suggest that the impact of environmental factors among both populations may have been under-appreciated.

Genome Scan Among Nigerians Linking Blood Pressure to Chromosomes 2, 3, and 19

Abstract—An understanding of the genetic influences on hypertension would help unravel the pathophysiology of this complex disorder and improve our understanding of causal mechanisms. Contemporary technology makes it possible to examine enough genetic markers to support a generalized search across the entire genome for candidate regions. In the present study, a family set was recruited from southwest Nigeria, and 378 microsatellite markers were typed on 792 individuals in 196 families. Multipoint variance component analysis identified linkage signals (logarithm of the odds [LOD] 1.74, P <0.0023) for systolic blood pressure on 19p (D19S714) and 19q (D19S246), whereas for diastolic blood pressure, linkage was observed on 2p (D2S1790), 3p (D3S1304), 5q (D5S1462), 7p (D7S3046), 7q (D7S821), and 10q (D10S1221). Other regions of interest (1.18<LOD<1.74, 0.0023<P <0.01) were found on chromosomes 1, 6, 8, 9, and 11. These results provide additional evidence of linkage between blood pressure and several genomic regions reported in previous studies. Some of these regions additionally harbor hypertension candidate genes. Although evidence of linkage for blood pressure has been very slow to accumulate, even in comparison to other complex traits, the sum of current evidence appears to implicate, in particular, 2p, 3p, and 19p. Study designs that make it possible to confirm these results with association analysis and narrow the genomic interval are needed in order to make progress in this field.

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people.

OBJECTIVE: The mean values for anthropometric traits vary across population groups and this variation is clearly determined for the most part by the environment. The familiarity of anthropometric traits also varies in reports from different populations, although this variation has not been shown to follow a consistent pattern. To examine whether heritability is influenced by socio-cultural factors, we conducted a cross-cultural study of populations of the African diaspora.PARTICIPANTS: Data were collected on 1868 family members from Nigeria, 623 from Jamaica and 2132 from metropolitan Chicago, IL, USA.MEASUREMENTS: Height and weight were measured and body mass index (kg/m2) calculated. Fat-free mass, fat mass and percentage body fat were estimated using bioelectrical impedance analysis. Plasma leptin concentrations were also measured. The proportion of variance attributable to additive genetic and non-shared environmental components was estimated with the maximum likelihood variance decomposition method.RESULTS: Mean values for all anthropometric traits increased along the socio-cultural gradient, and obesity increased from 5% in Nigeria to 23% in Jamaica and 39% in the USA. Within populations the relationships among traits both within individuals and within families were highly consistent. Heritability estimates for weight, body mass index, fat mass and percentage body fat were approximately 50% for all groups. Heritability for height was lower in Nigeria (62%) than in Jamaica (74%) or the US (87%).CONCLUSION: The familial patterns of body size and energy storage appear to be consistent in these genetically related populations across a wide range of environmental conditions.

Epidemiology, Heritability and Genetic Linkage of C-Reactive Protein in African-Americans (From the Jackson Heart Study)

C-reactive protein (CRP) has been studied largely in white non-Hispanic cohorts. There is limited information on CRPs range of values, heritability, and relation to cardiovascular disease risk factors in African Americans. The aim of this study was to evaluate the distribution, clinical correlates, heritability, and genetic linkage of log-transformed CRP in participants in the middle-aged to elderly African American cohort in the community-based Jackson Heart Study. The distribution and correlates of CRP were analyzed for the entire study cohort who underwent the first examination (2001 to 2004). Heritability was estimated for the family cohort nested within the larger Jackson Heart Study (246 families, n = 1,317). The relation between CRP and cardiovascular disease risk factors was tested with multivariable stepwise regression analyses. Heritability was estimated using a variance-components method. Linkage analysis was performed using the multipoint variance-components approach. The study sample consisted of 4,919 participants (mean age 55 +/- 13 years, 63% women); the median CRP concentration was 2.7 mg/L. In stepwise models, traditional risk factors explained 23.8% of CRPs variability, with body mass index (partial R(2) = 13.6%) explaining 57.1% of the variability of CRP due to traditional risk factors. The heritability of CRP (adjusted for age, gender, and body mass index) was 0.45. The strongest linkage evidence for CRP was observed on chromosome 11 (11p13 to 11p11.2), with a logarithm of odds score of 2.72. In conclusion, in this large population-based cohort of African Americans, circulating CRP concentration was heritable and associated with several traditional cardiovascular risk factors, particularly body mass index.

A randomized trial on sodium reduction in two developing countries

Hypertension remains the most common cardiovascular risk factor in developing countries, yet the majority of patients have no access to pharmacological therapy. Population-wide preventive strategies, such as salt restriction, are an attractive alternative, but experience in resource-poor settings is limited. To address this question, we conducted a randomized crossover study of salt restriction in adults living in Nigeria and Jamaica in order to estimate the mean blood pressure (BP) response. After a 4-week run-in period to determine willingness to adhere to a low-salt diet, 56 Jamaicans and 58 Nigerians completed an 8-week crossover study of low-salt and high-salt intake. Baseline BPs were in the normotensive range (systolic=125 mmHg in Jamaica, 114 mmHg in Nigeria). Baseline urinary sodium excretion was 86.8 and 125.6 mEq/day in Nigeria and Jamaica, respectively. The mean difference between urinary sodium excretion at baseline and at the end of the 3-week low-sodium phase was 33.6 mEq/day in Nigeria and 57.5 mEq/day in Jamaica. During the high-sodium phase, mean change in urinary sodium excretion from baseline to week 3 was 35.0 and 5.5 mEq/day in Nigeria and Jamaica, respectively. The mean change in systolic BP (‘high’ vs ‘low’ sodium phase) was approximately 5 mmHg in both groups. This study suggests that the efficacy of sodium reduction in developing countries equals those noted in more affluent cultures. If promoted on a wide scale, sodium reduction could be used to treat persons with established hypertension, and more importantly, to prevent age-related increases in BP in poor communities.

A genome-wide scan for quantitative trait loci linked to obesity phenotypes among West Africans

OBJECTIVE:To identify quantitative trait loci (QTL) for three obesity phenotypes: body mass index (BMI), fat mass (FM) and percent body fat (PBF) in West Africans with type 2 diabetes (T2DM).DESIGN:An affected sibling pair (ASP) design, in which both siblings had T2DM. Obesity was analyzed as a quantitative trait using a variance components approach.SUBJECTS:Sib-pairs affected with T2DM from the Africa America Diabetes Mellitus (AADM) study, comprising 321 sibling pairs and 36 half-sibling pairs.MEASUREMENTS:Weight was measured on an electronic scale to the nearest 0.1 kg, and height was measured with a stadiometer to the nearest 0.1 cm. Body composition was estimated using bioelectric impedance analysis (BIA). Genotyping was carried out at the Center for Inherited Disease Research (CIDR) with a panel of 390 trinucleotide and tetranucleotide repeats.RESULTS:The obesity-related phenotype showing the strongest linkage evidence was PBF on chromosome 2 (LOD 3.30 at 72.6 cM, marker D2S739). Suggestive linkage to FM was found on chromosomes 2 (LOD 2.56 at 80.4 cM) and 5 (LOD 2.25 at 98 cM, marker D5S1725). The highest LOD score for BMI was 1.68 (chromosome 4, 113.8 cM). The areas of linkage for the three phenotypes showed some clustering as all three phenotypes were linked to the same regions of 2p13 and 5q14, and our study replicated linkage evidence for several regions previously reported in other studies.CONCLUSION:We obtained evidence for several QTLs on chromosome 2, 4 and 5 to three obesity phenotypes. This study provides data on the genetics of obesity in populations that are currently under represented in the global effort directed at understanding the pathophysiology of excess adiposity in free living individuals.

Rapid increases in obesity in Jamaica, compared to Nigeria and the United States

BackgroundWeight gain in adulthood is now common in many populations, ranging from modest gains in developing countries to a substantial percentage of body weight in some Western societies. To examine the rate of change across the spectrum of low to high-income countries we compared rates of weight change in samples drawn from three countries, Nigeria, Jamaica and the United States.MethodsPopulation samples from Nigeria (n = 1,242), Jamaica (n = 1,409), and the US (n = 809) were selected during the period 1995–1999 in adults over the age of 19; participation rates in the original survey were 96%, 60%, and 60%, respectively. Weight in (kg) was measured on 3 different occasions, ending in 2005. Multi-level regression models were used to estimate weight change over time and pattern-mixture models were applied to assess the potential effect of missing data on estimates of the model parameters.ResultsThe unadjusted weight gain rate (standard error) was 0.34(0.06), 1.26(0.12), 0.34(0.19) kg/year among men and 0.43(0.06), 1.28(0.10), 0.40(0.15) kg/year among women in Nigeria, Jamaica, US, respectively. Regression-adjusted weight change rates were significantly different across country, sex, and baseline BMI. Adjusted weight gain in Nigeria, Jamaica and US was 0.31(0.05), 1.37(.04), and 0.52(0.05) kg/year respectively. Women in Nigeria and the US had higher weight gains than men, with the converse observed among Jamaicans. The obese experienced weight loss across all three samples, whereas the normal weight (BMI < 25) had significant weight gains. Missing data patterns had an effect on the rates of weight change.ConclusionWeight change in sample cohorts from a middle-income country was greater than in cohorts from either of the low- or high-income countries. The steep trajectory of weight gain in Jamaica, relative to Nigeria and the US, is most likely attributable to the accelerating effects of the cultural and behavioral shifts which have come to bear on transitional societies.

Energy Expenditure and Adiposity in Nigerian and African American Women

Objective: Obesity is a prevalent condition in industrialized societies and is increasing around the world. We sought to assess the relative importance of resting energy expenditure (REE) and activity EE (AEE) in two populations with different rates of obesity.

The distribution and mortality impact of chronic energy deficiency among adult Nigerian men and women

Objective: To determine the prevalence of chronic energy deficiency (CED) and associated mortality risk in a cohort of adult Nigerians followed from 1992 to 1997.Research methods and procedures: The data for this investigation were derived from an international collaborative study on chronic diseases in populations of the African diaspora. Body mass index (BMI) was used to define three grades of CED in 4061 men and women aged 25 years and older: Grade I (mild CED) as BMI 17.5–18.4, Grade II (moderate CED) as BMI 16.0–17.4, and Grade III (severe CED) as BMI<16.0 and BMI ≥18.5 was considered normal. The odds of mortality associated with differing grades of CED was estimated with logistic regression analysis.Results: The prevalence of CED (BMI<18.5) increased from 14.3% in 1992 to 19.6% in 1997, both genders combined. The prevalence of CED was similar for both sexes in 1992 (14%) but increased to 22.4% in men and 17.4% in women by 1997. The prevalence of CED was 8.5%, 7.6 and 3.4 for Grades I, II and III, respectively. Two hundred and seven deaths occurred during the follow-up period. The mortality rate for the 5.5u2005y of follow-up was 5.1% (207/4061). The odds ratios (95% Cls) for all cause mortality were 1.4 (0.5, 3.8), 2.4 (1.2, 4.9) and 2.5 (1.0, 6.2), respectively, for CED grades I, II and III adjusting for age and sex.Conclusion: Under nutrition is an increasing problem in Nigerian men and women. The economic reforms (structural adjustment program (SAP)) introduced in 1986 in combination with the continued economic woes brought on by political instability, corruption and nepotism have been advanced by several investigators as the main factors in the growing problem of inadequate calorie intake. Intervention strategies both at the government and private sectors are urgently needed to increase food availability.Sponsorship: This work was supported by grants from the National Institutes of Health (HL 45508, HL 47910, HL 53353).